van Emmerik N E, Vaessen L M, Knoop C J, Daane C R, Balk A H, Mochtar B, Claas F H, Weimar W
Department of Internal Medicine I, University Hospital-Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
Transpl Immunol. 1998 Sep;6(3):153-60. doi: 10.1016/s0966-3274(98)80040-3.
Studies on graft infiltrating cells demonstrated that accumulation of cytotoxic T lymphocytes (CTL) with high avidity for donor antigens (Ag) coincided with acute cardiac rejection. In the present study, we analyse whether such high-avidity CTL are present within the peripheral blood of cardiac transplant recipients and whether their kinetics correspond with the rejection status of the allograft. Using limiting dilution analysis (LDA), donor-specific CTL were enumerated in serial blood samples of seven patients. From each patient, 7-11 samples were obtained during the first year after transplantation and up to three samples were obtained at a later date. Enumerated donor-specific CTL were divided into CTL with high or low avidity for donor Ag, depending on their sensitivity to CD8-blocking. In contrast to the situation in the graft, the donor-specific CTL present within the peripheral blood were CTL precursors (pCTL) and not fully mature CTL (cCTL). The number of donor-specific pCTL among peripheral blood cells fluctuated irrespective of the rejection grade of the allograft, indicating that the frequency of circulating donor-specific CTL does not reflect the immunological status of the allograft. During acute cardiac rejection, 66% (median) of the circulating donor-specific pCTL had a high avidity for donor Ag. This percentage significantly exceeded pre- and postrejection values obtained during the first year post-transplantation (median, 39% and 37%, respectively). The disparity in avidity increased even further more than 1 year after transplantation, when stable engraftment was achieved. Among donor-specific pCTL in peripheral blood, those with a high avidity were absent (median, 0%). Hence the avidity of circulating donor-specific CTL might inform us about the immune status of the cardiac allograft.
对移植物浸润细胞的研究表明，对供体抗原（Ag）具有高亲和力的细胞毒性T淋巴细胞（CTL）的积累与急性心脏排斥反应同时发生。在本研究中，我们分析了心脏移植受者外周血中是否存在这种高亲和力CTL，以及它们的动力学是否与同种异体移植物的排斥状态相对应。使用极限稀释分析（LDA），在7名患者的系列血样中对供体特异性CTL进行计数。在移植后的第一年，从每位患者获取7 - 11份样本，后期最多获取3份样本。根据对CD8阻断的敏感性，将计数的供体特异性CTL分为对供体Ag具有高亲和力或低亲和力的CTL。与移植物中的情况不同，外周血中存在的供体特异性CTL是CTL前体（pCTL），而非完全成熟的CTL（cCTL）。外周血细胞中供体特异性pCTL的数量波动，与同种异体移植物的排斥等级无关，这表明循环中供体特异性CTL的频率不能反映同种异体移植物的免疫状态。在急性心脏排斥反应期间，循环中66%（中位数）的供体特异性pCTL对供体Ag具有高亲和力。该百分比显著超过移植后第一年排斥反应前和排斥反应后的数值（中位数分别为39%和37%）。移植1年多后，当实现稳定植入时，亲和力差异进一步增大。在外周血中供体特异性pCTL中，高亲和力的细胞不存在（中位数为0%）。因此，循环中供体特异性CTL的亲和力可能为我们提供关于心脏同种异体移植物免疫状态的信息。
